Endurance Training Reprograms The White Adipose Tissue Proteome Of Rats In A Sex-specific Manner

Abstract

mTOR is an established anabolic signaling that leads to skeletal muscle hypertrophy when activated. Hippo signaling is an emerging pathway that involves the muscle size change in response to resistance-type exercise. However, whether the Hippo signaling response differs in muscle-wasting conditions is unknown. PURPOSE: The purpose of this study was to determine whether repeated muscle contractions would induce different Hippo signaling responses in cachectic mice. METHODS: Male ApcMin/+ (Min, n=5) mice and age-matched Wild-type (WT, n=5) mice were used. A single bout of high-frequency electric stimulations (HFES, ten sets of six repetitions, ~18 min) was applied to both groups' tibialis anterior (TA) muscles. This intervention caused eccentric contraction on the left TA muscle, while the right TA muscle served as internal control. Both TA muscles were exercised and snap-frozen in the liquid nitrogen for further analysis after 30 min following the HFES. Routine western blotting was performed using approximately 60~120 µg of the total protein. Body and muscle weights were analyzed by a Student's t-test. Western blot data were analyzed by a two-way ANOVA with repeated measures (genotype x HFES). Post-hoc analyses were performed with the Bonferroni test when appropriate. RESULTS: Min mice lost approximately 17.6% of body weight (BW) than their peak BW at HFES, confirming that the Min mice had developed a cachectic condition. Min mice had a smaller TA weight than WT mice regardless of HFES (52.4±1.0 mg vs. 35.1±1.9 mg, p<0.01). Western blot analysis showed that HFES increased the phosphorylated state of p70S6K regardless of genotype (p<0.01). However, the p70S6K response to HFES was higher in WT mice than Min mice (2.5 folds vs. 1.5 folds, p<0.01). HFES decreased the activity levels of MOB1, a molecule of Hippo signaling, regardless of genotype (p<0.05), yet the Min mice maintained higher levels of MOB1 activity irrespective of HFES (p<0.05). The Hippo signaling effector YAP activity increased in response to HFES in WT mice, but not in Min mice (14.7% vs. 0.0%, p<0.05). CONCLUSION: These results suggest that the Hippo signaling response to muscle contractions differs between healthy and cachectic muscles in mice. Supported by the Louisiana Board of Regents Support Fund (LEQSF(2017-20)-RD-A-22).